Coronary angiography provides anatomical information which only partially predicts prognosis and response to therapy. A reliable and practical method for quantifying absolute regional myocardial perfusion and coronary vascular reserve in man has been developed. Digital coronary angiography produces high resolution images of contrast material transit through the coronary microcirculation from which regional iodine time-density curves can be quantified and in theory allows regional perfusion to be calculated. Conventional indicator dilution analysis of these curves has been limited because: the derived parameters are arbitrary descriptors of the shape of the regional dilution curves; they are greatly influenced by instrumentation noise and densitometric errors; and the shape, rate, concentration and timing of the contrast bolus injection is so critical that standardized intracoronary power injections are mandatory. The long range purpose of this grant is to solve these problems by modeling the coronary circulation as a linear system. To evaluate this possibility we have established five goals: 1. To develop linear analytical algorithms to quantify contrast material transit. through the coronary circulation; 2. To determine if the coronary circulation behaves as a linear system thereby permitting linear analysis; 3. To establish the regional accuracy and reproducibility for measuring perfusion and coronary flow reserve in canine and porcine models; 4. To develop a tool to quantify coronary physiology and the response to pharmacologic and mechanical interventions in the intact circulation; and 5. To validate these methods and develop clinical applications in man. Digital coronary angiography will be used to acquire time-density curves over the proximal coronary arteries and regional myocardial microcirculation. The system impulse response function will be computed by iterative convolution of these data with a lagged- normal density compartmental model of contrast material transit. Compartmental mean transmit times will be compared with regional myocardial perfusion and coronary flow reserve. The potential health-related benefits of this research are improved diagnostic and clinical decision making capability from coronary angiography by quantitative assessment of the functional significance of atherosclerotic coronary artery disease.